Animal models for AIDS are needed to study the pathogenesis of disease and to facilitate the development of vaccines. Although HIV infection of chimpanzees will undoubtedly make important contributes to these studies, this chimpanzee model will be practical only for a small number of applications. The staggering cost and limit availability of chimpanzees severely restrict their use for AIDS research. Simian immunodeficiency virus (SIV) infection of macaques provides an alternative mechanism by which in vivo studies can be performed. SIV is similar to the human virus in its biological properties, it is related in sequence to HIV and it induces in common rhesus monkeys a disease with remarkable similarities to AIDS in man. In the proposed experiments, vaccine-related developments in the laboratory will be quickly extrapolated to the SIV system. For example, if a BCG cloning and expression system is developed, it will be used to express SIV proteins and tested for vaccine potential in macaques. Neutralizing epitopes of SIV will identified and their importance in vaccine protection against SIV infection will be explored. Replication competent, deletion mutant strains of SIV will be identified which are attenuated for pathogenicity or persistence in vivo: attenuated strains of SIV which have lost their ability to persist in vivo will be tested as live virus vaccines in macaques. Results in the SIV system should suggest reasonable approaches for human AIDS prevention.